Growth dynamics of the vestibular schwannoma

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Abstract

Introduction: Studies concerning vestibular schwannoma (VS) are inconsistent in
reporting of tumor size and growth. This means that results found in one paper using
one set of definitions cannot be compared directly with results found in another paper
with another set of definitions. It is a challenge to make clinical decisions from studies
with such disparate definitions, as it is difficult to know how reliable the individual
findings are. This thesis thus aimed to empirically evaluate these different means of
reporting tumor size and growth that can be found in the literature. In addition to this,
we also present our own findings of the growth dynamics and predictors of untreated
VS, as well as evaluating the treatment outcome and complication rates for tumors
treated by gamma knife radiosurgery (GKRS).
Methods: The management of VS patients is determined primarily based on the tumor
size and observed tumor growth. The smallest tumors are conservatively treated by
serial scans, and if growth is detected, they are offered active treatment by either
microsurgery or GKRS. The papers in this thesis primarily focus on the conservatively
treated cohort, and those among them that were later treated by GKRS. Tumor
volumes were estimated by manual tracing on MRI. Mixed effects modeling was used
to analyze relationships between observations.
Results: The papers included in this thesis present a number of results. The first paper found several inherent flaws with the most commonly used
measure, the maximum diameter. Empirical proportionality coefficients which
were quite similar to theoretical values used in the literature were also found. The second paper showed that tumor growth was best described by volume
doubling time (VDT) rather than in terms of mm/year. We found a VDT of 4.40
years among our cohort. We also discussed the use of a cutoff of 1 mm/year to
distinguish between growing and non-growing tumors, and proposed a VDT
cutoff of 5.22 years that could be used similarly. None of the baseline
parameters investigated were predictive of tumor growth. The third paper described the risk of needing treatment with the wait-and-scan
protocol to be 13.3% at two years, and 41.3% at five years. The study also
found a decline of hearing function for conservatively managed patients.
Neither tinnitus nor unsteadiness changed significantly from baseline, but there
was a reduction in the number of patients reporting vertigo. Results also suggest
that tumor growth may be associated with progression of tinnitus and imbalance
problems. The fourth paper found a radiological tumor control rate of 71.1%. Higher age
and larger tumor size were found to be positively associated with tumor control.
Hearing was preserved in 79% of the patients who had serviceable hearing at
the time of treatment. Permanent facial weakness as a result of GKRS treatment
occurred in one patient. In terms of QoL, bodily pain and general health scores
improved significantly after GKRS. Social function steadily declined
throughout the follow-up period, which may be related to the increasing
number of patients experiencing unilateral hearing loss. Conclusion: In the discussion of inconsistencies in reporting of tumor size and tumor
growth, our studies propose that there exist both empirical and biological arguments
for the use of volumes and VDT’s rather than diameters and linear growth rates. A
VDT cutoff of 5.22 years can distinguish between clinically growing and non-growing
tumors. Our findings support the continued use of a conservative approach among
small, non-growing tumors. For medium-sized or growing tumors, we also suggest
that GKRS is a preferable treatment to microsurgery, given the high tumor control rates and low rates of complication with GKRS. The tumor control can also be
improved by taking into consideration the potential predictors found in our study when
selecting patients for this treatment, namely the patient’s age and the tumor size
(although from a radiobiological point of view, one would expect the opposite effect
from these parameters). Several scales of QoL were also found to improve
significantly after GKRS, thus supporting the practice of recommending this form of
treatment to these tumors. The social function scale however got steadily worse from
baseline.

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Paper I: Varughese JK, Wentzel-Larsen T, Vassbotn F, Moen G, Lund-Johansen M. Analysis of vestibular schwannoma size in multiple dimensions: a comparative cohort study of different measurement techniques. Clinical Otolaryngology 35(2): 97-103, April 2010. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.1111/j.1749-4486.2010.02099.x